Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) Complicated by Generalized Tonic-Clonic Seizures After a Course of Antibiotics: A Case Report.

Nitrofurantoin and cephalexin are commonly used antibiotics for treating urinary tract infections. Hyponatremia secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been reported as a rare side effect of nitrofurantoin but has never been a reported side effect of cephalexin. We report a case of a 48-year-old female who developed severe hyponatremia complicated by generalized tonic-clonic seizures after a course of antibiotics (nitrofurantoin followed by cephalexin) used for treating a urinary tract infection. She presented to the emergency department with a one-week history of dizziness, nausea, fatigue, and listlessness. She also had a two-week history of persistent urinary frequency despite completing a course of nitrofurantoin followed by a course of cephalexin. While in the emergency department waiting room, she had two episodes of generalized tonic-clonic seizures. Immediate post-ictal blood test results revealed severe hyponatremia and lactic acidosis. Results were consistent with severe SIADH and she was subsequently managed with hypertonic saline and fluid restriction. She was discharged after 48 hours of admission when her serum sodium levels normalized. Though we believe that nitrofurantoin was the culprit drug, we still asked the patient to avoid future use of both nitrofurantoin and cephalexin. Healthcare providers need to be aware of antibiotic-induced SIADH when assessing patients with hyponatremia.

Recurrent Gestational Thrombocytopenia Affecting Four Consecutive Pregnancies: A Case Report.

Gestational thrombocytopenia is the commonest cause of thrombocytopenia in pregnancy, accounting for 70-80% of cases. It is a benign condition that recovers completely in the postpartum period. Although the cause is not fully understood, it is thought that pregnancy-related hemodilution and increased platelet consumption play a significant contributory role. Several life-threatening causes of thrombocytopenia in pregnancy make up the remaining 20-30% of cases. There are reports of recurrence of GT in women, but not many case reports document more than three consecutive episodes. We present a case of a young woman who had gestational thrombocytopenia during the third trimester of her four consecutive pregnancies, followed by complete recovery after each pregnancy. We ruled out other sinister and life-threatening causes of thrombocytopenia in pregnancy. During her four consecutive pregnancies, her platelet count fell below normal at the beginning of the third trimester, with a nadir towards the end. The other hematological indices, generally used as markers of hemodilution, remained in the normal pregnancy-specific reference range during each of her four pregnancies. This case argues against pregnancy-related hemodilution being a major factor in gestational thrombocytopenia. A systematic approach is paramount when differentiating the several causes of thrombocytopenia in pregnancy.

A Rare Case of Severe Hemolytic Anemia and Pulmonary Embolism Secondary to Mycoplasma pneumoniae Infection.

A 27-year-old woman was admitted with a history of dry cough, breathlessness, fever, lethargy, and nausea and vomiting. On examination, she was febrile, jaundiced, and hypoxic. Blood tests revealed severe leucocytosis and severe hemolytic anemia. The chest imaging demonstrated coexisting pneumonia and pulmonary embolism. An initial blood transfusion worsened the hemolytic anemia to the point that critical care review was required. Subsequent blood tests revealed cold agglutinin hemolytic anemia due to Mycoplasma pneumoniae infection. The patient's condition improved after receiving a warm-blood transfusion, antibiotics, and steroid therapy. The patient also received anticoagulant therapy for 6 months. Our case is unique in that the patient had very severe anemia and very severe leucocytosis, making us suspect a hematologic malignancy at initial presentation. This case emphasizes the importance of prompt evaluation of hemolytic anemia and the use of warm blood transfusion for cold agglutinin disease.

Biochemical transition during triphasic postpartum thyroiditis: confusion with central hypothyroidism.

SUMMARY: Hypothyroidism occurring in the postpartum period can be due to pituitary or hypothalamic disease as in Sheehan's syndrome and postpartum autoimmune hypophysitis or due to a primary thyroid disease as in postpartum thyroiditis. It is important that the correct diagnosis is ascertained because hypothalamic or pituitary disorders are often associated with other pituitary hormone deficiencies, especially life-threatening adrenal insufficiency or adrenal crisis. A combination of various symptoms and biochemical markers, especially serum thyroid-stimulating hormone levels dictate the initial diagnostic pathway. We present a case of a woman who presented with a 2-month history of tiredness and neck discomfort following delivery. A thyroid function test demonstrated results, which we initially interpreted as central hypothyroidism. Follow-up results indicated that this was in fact the transition period between the thyrotoxic phase and hypothyroid phases of postpartum thyroiditis. This case highlights the potential for diagnostic confusion between central hypothyroidism and postpartum thyroiditis. LEARNING POINTS: Postpartum thyroiditis affects one in twenty mothers within 12 months of delivery. The majority of patients have transient thyrotoxicosis only, some have transient hypothyroidism only, and the rest has a triphasic pattern (thyrotoxic, hypothyroid then a euthyroid phase). During the transition from the thyrotoxic phase to hypothyroid phase, when serum TSH is still suppressed, the biochemical results can resemble that of central hypothyroidism. If central hypothyroidism is suspected, then urgent diagnostic investigations should be carried out along with the assessment of adrenal function. There is a potential for diagnostic confusion between postpartum central hypothyroidism and postpartum thyroiditis; however, the obstetric history, clinical symptoms, and signs (headaches, breastfeeding, goitre, etc.) and serum adrenocorticotropic levels should help with the differential diagnosis.

Bilateral Testicular Epidermoid Cysts in a Man with Klinefelter Syndrome: A Case Report.

Klinefelter syndrome is a rare chromosomal disorder with at least one extra X chromosome in males resulting in male hypogonadism, androgen deficiency and impaired spermatogenesis. It is associated with an increased risk of certain malignancies; including leukemia, breast cancer, non-Hodgkin's lymphoma and mediastinal germ cell tumors, however, testicular tumors are rare in men with Klinefelter syndrome. Testicular epidermoid cysts are rare benign tumors affecting the testes. We report a case of bilateral testicular epidermoid cysts in a 30-year-old man known to have Klinefelter syndrome. He had an incidental finding of bilateral hard irregular-surfaced testes during routine assessment for testosterone replacement therapy. Biochemical investigation confirmed primary hypogonadism and ultrasound imaging demonstrated bilateral solid testicular masses with no blood flow seen within the lesions. The patient went on to have a right-sided radical orchiectomy with left-side sparing. The histology revealed features in keeping with that of a testicular epidermoid cyst with no evidence of malignancy. The patient was commenced on testosterone replacement therapy. This case emphasizes the importance of routine physical examination of the male external and internal genitalia when considering testosterone replacement therapy.

Normosmic idiopathic hypogonadotropic hypogonadism due to a novel GNRH1 variant in two siblings.

SUMMARY: Hypogonadotropic hypogonadism is characterised by insufficient secretion of pituitary gonadotropins resulting in delayed puberty, anovulation and azoospermia. When hypogonadotropic hypogonadism occurs in the absence of structural or functional lesions of the hypothalamic or pituitary gland, the hypogonadism is defined as idiopathic hypogonadotropic hypogonadism (IHH). This is a rare genetic disorder caused by a defect in the secretion of gonadotropin releasing hormone (GNRH) by the hypothalamus or a defect in the action of GNRH on the pituitary gland. Up to 50% of IHH cases have identifiable pathogenic variants in the currently known genes. Pathogenic variants in the GNRHR gene encoding the GNRH receptor are a relatively common cause of normosmic IHH, but reports of pathogenic variants in GNRH1 encoding GNRH are exceedingly rare. We present a case of two siblings born to consanguineous parents who were found to have normosmic idiopathic hypogonadotropic hypogonadism due to homozygosity of a novel loss-of function variant in GNRH1. Case 1 is a male who presented at the age of 17 years with delayed puberty and under-virilised genitalia. Case 2 is a female who presented at the age of 16 years with delayed puberty and primary amenorrhea. LEARNING POINTS: IHH is a genetically heterogeneous disorder which can be caused by pathogenic variants affecting proteins involved in the pulsatile gonadotropin-releasing hormone release, action, or both. Currently known genetic defects account for up to 50% of all IHH cases. GNRH1 pathogenic variants are a rare cause of normosmic IHH. IHH is associated with a wide spectrum of clinical manifestations. IHH can be challenging to diagnose, particularly when attempting to differentiate it from constitutional delay of puberty. Early diagnosis and gonadotrophin therapy can prevent negative physical sequelae and mitigate psychological distress with the restoration of puberty and fertility in affected individuals.

A rare coexistence of Behcet's disease and Graves' thyrotoxicosis in a young man: a case report.

Behcet's disease is a recurrent systemic vasculitic disorder. It manifests most commonly in the form of skin lesions, oral and genital ulcers and uveitis. Graves' thyrotoxicosis is an autoimmune disorder characterized by excessive production of thyroid hormones. We present a case of a 41-year-old male of Turkish descent who had symptoms of arthralgia, rash, palpitations and weight loss. Bloods tests showed raised inflammatory markers and biochemical evidence of severe autoimmune thyrotoxicosis. The patient was HLA-B51-negative, and pathergy test was inconclusive. A diagnosis of Behcet's disease was made on constellation of clinical symptoms. The patient was treated with carbimazole and prednisolone followed by azathioprine. The coexistence of Behcet's disease and Graves' disease in the same patient is very rare. Further studies are required to determine if there is a pathological association between these two conditions.

Leucine-rich glioma-inactivated protein 1 (LGI-1) mediated limbic encephalitis associated with syndrome of inappropriate antidiuretic hormone secretion: a case report.

Autoantibodies to leucine-rich glioma-inactivated protein 1 (LGI-1) are associated with inflammation of the limbic system. Faciobrachial dystonic seizures are pathognomonic for LGI1-antibiodies and their treatment with immunotherapy is effective in seizure control with a potential to prevent cognitive decline. We report a 57-year-old man who presented to the emergency department with recurrent seizures, visual hallucinations and severe memory impairment over a seven-week period; he reported a background of alcohol excess. Initial investigations revealed hyponatremia, indicating syndrome of inappropriate anti-diuretic hormone secretion. Magnetic resonance imaging of the brain revealed bilateral asymmetrical high-T2 and low-T1 signal in the medial temporal lobes. Serum immunofluorescence assay tested positive for LGI-1 antibody. Patient responded to treatment with levetiracetam, intravenous methylprednisolone and five plasma exchange sessions. Patient remains on a maintenance dose of prednisolone and azathioprine. It is imperative that clinicians recognize signs of autoimmune encephalitis in order to curb long-term sequelae and improve clinical outcomes.

A novel CASR variant in a family with familial hypocalciuric hypercalcaemia and primary hyperparathyroidism.

SUMMARY: Familial hypocalciuric hypercalcaemia (FHH) is a dominantly inherited, lifelong benign disorder characterised by asymptomatic hypercalcaemia, relative hypocalciuria and variable parathyroid hormone levels. It is caused by loss-of-function pathogenic variants in the calcium-sensing receptor (CASR) gene. Primary hyperparathyroidism (PHPT) is characterised by variable hypercalcaemia in the context of non-suppressed parathyroid hormone levels. Unlike patients with FHH, patients with severe hypercalcaemia due to PHPT are usually symptomatic and are at risk of end-organ damage affecting the kidneys, bone, heart, gastrointestinal system and CNS. Surgical resection of the offending parathyroid gland(s) is the treatment of choice for PHPT, while dietary adjustment and reassurance is the mainstay of management for patients with FHH. The occurrence of both FHH and primary hyperparathyroidism (PHPT) in the same patient has been described. We report an interesting case of FHH due to a novel CASR variant confirmed in a mother and her two daughters and the possible coexistence of FHH and PHPT in the mother, highlighting the challenges involved in diagnosis and management. LEARNING POINTS: Familial hypocalciuric hypercalcaemia (FHH) and primary hyperparathyroidism (PHPT) can coexist in the same patient. Urinary calcium creatinine clearance ratio can play a role in distinguishing between PHPT and FHH. Genetic testing should be considered in managing patients with PHPT and FHH where the benefit may extend to the wider family. Family segregation studies can play an important role in the reclassification of variants of uncertain significance. Parathyroidectomy has no benefit in patients with FHH and therefore, it is important to exclude FHH prior to considering surgery. For patients with coexisting FHH and PHPT, parathyroidectomy will reduce the risk of complications from the severe hypercalcaemia associated with PHPT.

Difficult-to-treat Syndrome of Inappropriate Antidiuretic Hormone Secretion in a Patient with Secondary Central Nervous System Lymphoma.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is defined as hyponatremia with inappropriately concentrated urine in a euvolemic patient. SIADH is associated with a wide spectrum of clinical conditions. In the hospital, hyponatremia carries significant mortality with a prolonged duration of inpatient stay. It is imperative that the underlying cause is appropriately investigated and such patients are closely monitored. This article presents a case of difficult-to-treat hyponatremia secondary to SIADH in a patient with a rare isolated central nervous system (CNS) relapse from a non-Hodgkin's lymphoma (NHL). A relapse, particularly affecting the CNS, carries a poor prognosis. The patient was started on dexamethasone and offered treatment with methotrexate but declined. The hyponatremia failed to respond to fluid restriction and demeclocycline. The hyponatremia responded to a single dose of tolvaptan. Clinicians should have a low index of suspicion for a relapse of lymphoma as a cause of difficult to treat hyponatremia in any patient who has previously had remission from lymphoma treatment.